The fusion of calcium beta alanate with alpha-hydroxybeta, beta dimethyl-gamma-butyrolactone has been used to prepare calcium pantothenate. Another route is the reaction of beta-alanine with the lactone in aqueous calcium hydroxide. A direct fusion of the lactone with beta-alanine at about 150.degree. C produces pantothenic acid, according to U.S. Pat. No. 2,418,902 but the temperature must not be allowed to reach 200.degree. C because of decomposition detrimental to the purity of the end product. This reaction is only 17% complete. Also, the reaction of beta-alanine, calcium hydroxide and the lactone in an aliphatic alcohol solution is reported in British Pat. No. 561,877. Each of these processes require complicated purification procedures directed to the elimination of volatiles to prepare the dried salt. The British patent describes the preparation of crystalline calcium pantothenate by reaction of calcium metal with B-alanine in methanol solution to form solid calcium beta alanate for reaction with the lactone in isopropyl alchohol solution, the last step taking from 3 to 6 days.
U.S. Pat. No. 2,234,680 and 2,418,902 describe a more direct approach by reacting the lactone with beta alanine at about 178.degree. C to produce pure pantothenic acid for conversion directly to the calcium salt which can be administered in such form without the need for purification. The use of calcium oxide in the final stages to produce calcium pantothenate from the reaction of equimolecular amounts of the butyrolactone and beta alanine in anhydrous alcohol, in the presence of a molecular equivalent of a secondary or tertiary amine, described in U.S. Pat. No. 2,496,363 is time consuming, requires charcoal filtering and final seeding to precipitate the final product. Furthermore, the reaction produces one equivalent of water which contaminates any recovered alcohol and amine, which for re-use must first be dehydrated and interferes with the preparation of a dried crystalline product.
U.S. Pat. No. 2,809,213 by the instant inventor, represents an improvement over the process of U.S. Pat. No. 2,234,680 in that calcium metal is used in place of the calcium oxide, thus allowing the preparation of either an optically active form of the salt or its corresponding optically inactive racemic form. By way of explanation, the presence of an asymmetric carbon atom in pantothenic acid explains the fact that in the stable salts thereof there exists two optically active forms, one dextro-rotatory and the other levo-rotatory. The dextro-rotatory form is the most important of these two forms because it is biologically active while the levo-rotatory form is to the contrary, biologically inactive. In addition, there exists a third or racemic form which is optically inactive but biologically active to the extent of approximately one-half that of the corresponding dextro-rotatory form.
While the dextro-rotatory form of calcium pantothenate has a biological potency equivalent to approximately twice the same amount of racemic calcium pantothenate, nevertheless, the cost of preparation per unit weight of biologically active mass is far greater for the dextro-rotatory form as compared with the racemic form. This is due to the fact that it is necessary to use the relatively expensive levo-rotatory alpha-hydroxy-beta, beta-dimethyl-gamma-butyrolactone in the preparation of dextro-rotatory pantothenic acid salts which lactone is obtained by preparing derivatives of the synthetically produced racemic form of the lactone with an optically active base such as an alkaloid, and resolving the optically active isomers therefrom.